search this blog

Friday, October 31, 2014

The recent Gamba at el. paper on the genetic prehistory of the Great Hungarian Plain was an excellent piece of paleogenomic detective work. However, I feel that the authors could have done a little better with characterizing the genetic origins of their samples.

For instance, the Principal Component Analysis (PCA) appears to suffer from subtle projection bias, which is a common problem in ancient DNA studies (see here). Also, the model-based analyses, like the ADMIXTURE run, leave me wanting a lot more.

However, all of the samples are freely available online, including in user friendly genotype format at Genetic Genealogy Tools. So I thought it might be useful to take a closer look at three of the genomes, spanning a 2,000-year period from the Copper Age to the Iron Age: CO1, BR1 and IR1.

The metal ages are a critical period of prehistory and early history in the making of modern Europe. It's a time of profound cultural changes, and as we now know, large-scale genetic shifts across the continent (see here). Indeed, the three aforementioned genomes clearly show that major genetic shifts took place on the Great Hungarian Plain from the Copper Age to the Iron Age. However, they also suggest strong genetic continuity in the region throughout this period.

CO1, the Copper Age genome from a Baden Culture burial, appears ridiculously Western European, and could easily pass for a present-day Sardinian in most analyses, even though it's most likely of Balkan and Near Eastern origin. It's very similar in that respect to another Copper Age sample, Oetzi the Iceman from the Tyrolean Alps.

One of the main reasons for this Sardinian-like genetic character is certainly its very low level of Ancient North Eurasian (ANE) admixture, probably much less than five per cent. Almost everyone in West Eurasia has more these days, so they appear a lot more eastern.

BR1 represents the Early Bronze Age (EBA) Mako Culture. It looks roughly like a cross between CO1 and someone from northeastern Europe with an unusually high level of hunter-gatherer ancestry, and also a fair whack of ANE. Indeed, after running a variety of tests, I'd say that BR1 has around 12% of ANE (in other words, more than Basques but less than British, which fits with its position on the West Eurasian PCA).

So as far as I can see, the most parsimonious explanation for this result is a population movement into present-day Hungary from the northeast during the EBA, perhaps associated with the early Indo-Europeans and the not-so-pleasant effects of the 4.2 kiloyear event (see here).

Interestingly, the 4A Oracle suggests that BR1 might in large part be a mixture of CO1 and KO1, which is another sample from Gamba et al., assigned to the Koros Culture of early Neolithic Balkan farmers, but with typically hunter-gatherer genetic structure. This opens up the possibility that people with unusually high levels of hunter-gatherer ancestry lived on the Great Hungarian Plain throughout the Neolithic, and the sampling by Gamba et al. was too patchy to find them.

However, it's not possible to get a genome like BR1 simply by mixing CO1 with KO1, because the hunter-gatherer-like sample is not eastern enough. In other words, it lacks ANE. I know this just by eyeballing a couple of PCA, featuring KO1 and Motala12, a Scandinavian sample estimated by Lazaridis et al. to have a ratio of ~19% ANE (see here and here).

So there might well have been a resurgence in local hunter-gatherer DNA on the Great Hungarian Plain, and perhaps throughout much of Central Europe, after the Neolithic. Nevertheless, in my opinion this alone cannot explain the results in this case.

IR1, the Iron Age genome, is clearly mixed. In some ways, much like CO1 and BR1, it's also deceptively similar to present-day Western Europeans, which suggests that it's in large part of local origin. However, its uniparental markers (Y-haplogroup N-M231 and mitochondrial haplogroup G2a1) actually fit better in Siberia than anywhere in Europe, and its genome-wide DNA shows influences from the North Caucasus and Volga-Ural regions (refer to the 4A Oracle results below).

Because of its complex ancestry, I can't accurately estimate the level of ANE admixture in this genome. Nevertheless, the PCA and Eurogenes K15 suggest that it easily surpasses BR1 in this respect. Note, for instance, its position among the Kargopol Russians and North Ossetians on the global PCA plot, as well as its high Eastern Euro score in the Eurogenes K15.

What I think this hints at is that the present levels of ANE across Europe aren't the result of a single early Indo-European migration, but multiple population movements around the continent spanning the entire metal ages, although usually involving Indo-European groups, and the effects of isolation-by-distance.

By the way, IR1 comes from a burial site of the Mezocsat Culture, which is generally accepted to be of Cimmerian origin. The Cimmerians are usually described as a nomadic Indo-European people from the Kuban steppe, just north of the Caucasus, who were pushed west by the expanding Scythians. Apparently, they founded a variety of cultures in the Carpathian Basin and Balkans by imposing themselves as the ruling elite over the locals. It's remarkable how closely IR1's genetic structure fits this narrative.

Also, here's a really cool map of Identity-by-Descent (IBD) hits of over 3 cM shared between IR1 and a wide range of present-day populations. It comes from a recent post at Vadim's blog (see here). The shared IBD peaks are found in East Central Europe and the Volga-Ural region, which makes sense.

Sunday, October 26, 2014

Most visitors here are probably aware by now that the Iron Age genomes from Hinxton are the two male samples 1 and 4 (ERS389795 and ERS389798, respectively). You can find confirmation of this at the link below.

The researchers were surprised to find that the older Iron Age men were genetically more similar to people living in Britain today than the Anglo-Saxon women were. Stephan Schiffels of the Wellcome Trust Sanger Institute reported the results October 20 at the annual meeting of the American Society of Human Genetics.

“It doesn’t look like these Anglo-Saxon immigrants left a big impact on the genetic makeup of modern-day Britain,” Schiffels said.

The finding raises an intriguing possibility that indigenous people in Britain may have repelled the Anglo-Saxons but adopted the invaders’ language and culture, says Eimear Kenny, a population geneticist at the Icahn School of Medicine at Mount Sinai in New York City, who was not involved in the work. More ancient samples from other times and parts of Britain should give a clearer picture of that episode of history, she said.

In regards to the main thrust of the article above, I'm not sure if there's much point discussing whether the British today are mostly of Celtic or Anglo-Saxon stock based on just five ancient genomes from a single location in England. However, if I was told that Hinxton4, the only high coverage genome in this collection, was a modern sample, I'd say it belonged to an Irishman from western Ireland, rather than an Englishman from eastern England.

Thus, unless Hinxton4 was an ancient migrant from Ireland, then it does seem to me as if there was a fairly significant admixture event in England between the indigenous Irish-like Celts and newcomers from the east, which eventually resulted in the present-day English population.

In any case, there are indeed some noticeable differences between the two sets of samples, and these can be visualized by plotting their f3 shared drift statistics.

For instance, plotting the f3-statistics of Hinxton2, which actually looks like the genome of someone straight off the boat from the Jutland Peninsula, against those of Hinxtons 1 and 4, we see that the former shares most drift with the Danes. Moreover, the Danes, Swedes and Germans, all Germanic-speakers of course, deviate strongly on both graphs from the lines of slope that run from the Erzya to the Irish. The reason they deviate from these lines is because they don't share enough drift with Hinxtons 1 and 4 compared to the other reference populations from Northwestern Europe, especially the Irish.

A similar pattern can be seen when plotting the average results of Hinxtons 1 and 4 against those of 2, 3 and 5. However, the effect isn't nearly as pronounced, possibly because Hinxtons 3 and 5 are of mixed Celtic/Germanic origin.

Friday, October 24, 2014

Hinxton5, or ERS389799, is one of five ancient English genomes stored at the Sequence Read Archive under accession number ERP003900. However, this analysis is based on the genotype file of Hinxton5 available at Genetic Genealogy Tools. For more information and some speculation about these genomes see my earlier blog post here.

Despite its relatively low North Sea score in the Eurogenes K15, and pronounced western shift on the Principal Component Analysis (PCA) plots, this genome appears mostly Germanic. In my opinion, the shared drift stats and also oracle results are quite convincing in this regard. If this were a modern sample it could probably pass for 3/4 north Dutch and 1/4 Irish. By the way, the Sub-Saharan admixture just looks like noise; this is, after all, a low coverage genome.

Wednesday, October 22, 2014

Not long ago I predicted that Ust'-Ishim belonged to a basal form of Y-chromosome haplogroup P (see here). As it turns out, the 45,000 year-old western Siberian genome belongs to K(xLT) or K-M526, which is actually pretty close to my guess. The Ust'-Ishim paper was published today and is behind a paywall here, but the extensive supp info is free.

Here's a map to help visualize the information, featuring Ust'-Ishim as well as Mal'ta boy, another North Eurasian Upper Paleolithic genome published recently.

The Ust'-Ishim genome was sequenced from the fossil of a femur bone found on the right bank of the Irtysh River. This area is very close to the Urals, and almost in the middle of the former Mammoth steppe that once stretched across North Eurasia from Iberia to Alaska. Interestingly, M526 is an ancestral mutation to the markers that define Y-chromosome haplogroups N, Q and R, which possibly dominated North Eurasia since the Upper Paleolithic (note that the 24,000 year-old Mal'ta boy belongs to a basal form of R).

Moreover, R1a and R1b are the most frequent haplogroups in Europe today. Thus, it would seem that most European males derive their paternal ancestry from North Eurasian hunter-gatherers whose ancestors spread out across Eurasia from the Middle East over 45,000 years ago.

I know that a lot of people have been arguing recently that K-M526 and the derived P-M45 originated and diversified in Southeast Asia, and then migrated north well within the last 45,000 years (for instance, see here). However, considering that K-M526 was already in reindeer country 45,000 years ago, as well as the Denisovan (ancient Siberian hominin) admixture among Southeast Asians, that might well turn out to be the equivalent of arguing that up is down and down is up.

By the way, Ust'-Ishim also belongs to pan-Eurasian mitochondrial (mtDNA) haplogroup R*, and in terms of genome-wide genetic structure appears roughly intermediate between West and East Eurasians. These outcomes fit very nicely with its Y-haplogroup.

However, it's slightly closer to Mesolithic Iberian genome La Brana-1, Upper Paleolithic Siberian MA-1 (or Mal'ta boy), and present-day East Asians, than to present-day West Eurasians, including Europeans. That's because it lacks "ancestry from a population that did not participate in the initial dispersals of modern humans into Europe and Asia". This is obviously the so called Basal Eurasian admixture discussed in Lazaridis et al. (see here), which is probably associated with early Neolithic farmers.

Also worth mentioning is that Ust'-Ishim harbors longer stretches of Neanderthal chromosomal segments than present-day Eurasians, which suggests that admixture between modern humans and Neanderthals took place in the Middle East not long before the ancestors of Ust-Ishim moved into Siberia (50-60,000 years ago). But this was already covered months ago, and you'll find lots of links on the topic on Google.

Tuesday, October 21, 2014

This open access paper on the genetic prehistory of the Great Hungarian Plain is full of surprises. Here are a few of my observations:

- Four of the genomes from a Neolithic farming context produced two Y-haplogroups previously identified in Mesolithic European hunter-gatherers (I2a and C6), and one of the samples (KO1) could probably pass for a Mesolithic hunter-gatherer overall, suggesting that males of hunter-gatherer origin played a major role in early European Neolithic societies. But what's happened to the C6 since then?

- The two Bronze Age genomes, BR1 and BR2, look very present-day French, and probably western French at that, in both the Principal Component and Admixture analyses. Indeed, they clearly show a northern influence relative to all of the Neolithic farmers and the Iron Age IR1. And yet, BR2 belongs to Y-haplogroup J2a1, which is generally seen as a Near Eastern marker.

- IR1 is described as a pre-Scythian genome with both East Eurasian and North Caucasian affinities (it's not clear in the paper whether it belongs to Y-haplogroup N and mtDNA G2a1, or vice versa, although either way works in this context). However, it also shows significant Northern European-like ancestry, and is even inferred to have fair hair, which makes me think that its eastern shift might be in large part due to Eastern Hunter-Gatherer (EHG) or Yamnaya-related admixture, which is now pervasive across Northern Europe (see here).

- Many people, including myself nowadays, see the Carpathian Basin as potentially a major staging point for the expansion of Y-chromosome haplogroup R1b into Central and Western Europe during the Bronze Age. And yet, it's again missing from the line-up.

- The T allele at SNP rs4988235, associated with lactase persistence into adulthood in Europeans, is only present among the two most recent genomes: BR2 and IR1. This suggests that selection for this allele, which now reaches frequencies of well over 50% in much of Europe, post dates not only the Neolithic but also the early Indo-European period, and was possibly most intense during the metal ages.

- Some of the Neolithic samples are clearly shifted towards the Bedouins (Bed) in Figure 2, relative to Oetzi the Iceman, a Copper Age genome from the Tyrolean Alps, which is generally considered to be typical of European Neolithic farmers (see below). So perhaps further sampling of Neolithic remains from southern Europe, in particular the southern Balkans, might reveal early farmers who actually cluster with Near Eastern populations, rather than Europeans?

- The authors found a sweetspot for extracting ancient DNA from humans: "the petrous portion of the temporal bone, the densest bone in the mammalian body". The amount of endogenous DNA salvaged from this part of the skull exceeds those from other bones by up to 183-fold. This is obviously great news, and probably means we can expect many more ancient genomes to be published in the near future.

Monday, October 20, 2014

Several people tweeted from Iosif Lazaridis' talk at the ASHG earlier today, which focused on ancient DNA from 65 Neolithic and Bronze Age Europeans. Here are a couple of the tweets that caught my eye:

There was an influx from north Eurasian steppe into Europe after advent of farming. Consistent w linguistic evidence.Link

So it seems that latest paleogenomics data support the linguists and archeologists who see the Proto-Indo-European (PIE) homeland on the Eastern European steppe. For some background on that, check out the videos here.

Razib also tweeted a few times from the talk, and as far as I can tell, his main point was that the Yamnaya samples showed affinity to the Ancient North Eurasian (ANE) proxy Mal'ta boy, but were also partly of Near Eastern origin, and indeed could be modeled as a 50/50 mixture between present-day Armenians and ancient Karelian hunter-gatherers. He also said that the ancient Karelians were classified as eastern hunter-gatherers (let's call them EHG for now), along with the hunter-gatherers from the Samara Valley, which probably means they carried a lot of ANE admixture.

Moreover, he added that Corded Ware genomes from late Neolithic Germany could be modeled as 75% Yamnaya, while another source from the talk revealed to me that they carried a minimum of 36% EHG.

All of this makes sense, considering that during the Neolithic much of present-day Ukraine west of the Dnieper was home to the Cucuteni-Trypillian farmers, probably of Near Eastern origin, while at the same time large groups of indigenous hunter-gatherers still foraged east of the Dnieper. Based on archeological data, it seems these two groups mixed at some point, becoming mobile pastoralists associated with the Yamnaya culture, and then expanded in all directions during the late Neolithic/early Bronze Age, potentially spreading Indo-European culture and languages as they went.

The Cucuteni-Trypillian farmers might well have been very similar to present-day Armenians, although probably without the 10-15% of ANE carried by them, which likely arrived in eastern Anatolia with the early Indo-Europeans from the steppe.

By the way, it's possible that the Karelian hunter-gatherers are the same samples as those featured in Der Sarkissian et al. 2013., where they were reported to carry mitochondrial (mtDNA) haplogroups C1 (3 instances), U2e (x2), U4 (x2), U5a and H.

Here's a spatial map from that study showing genetic distances between the ancient Karelian mtDNA and that of modern populations.

Hinxton4, or ERS389798, is one of five ancient English genomes stored at the Sequence Read Archive under accession number ERP003900. However, this analysis is based on the genotype file of Hinxton4 available at Genetic Genealogy Tools. For more information and some speculation about these genomes see my earlier blog post here.

I still don't know who these samples represent exactly, but in all likelihood, this is one of the two Iron Age sequences from the collection, and probably belongs to a Briton of Celtic stock. Note, for instance, its high affinity to the present-day Irish, relatively low North Sea score in the Eurogenes K15, and pronounced western shift on the second Principal Component Analysis (PCA) plot below.

Interestingly, Lithuanians top its shared drift list based on the Human Origins dataset and more than 360K SNPs. I'm not entirely sure what this means, but it's probably related in some way to the unusually high level (>45%) of indigenous European hunter-gatherer ancestry carried by Lithuanians.

Friday, October 17, 2014

Hinxton3, or ERS389797, is one of five ancient English genomes stored at the Sequence Read Archive under accession number ERP003900. However, this analysis is based on the genotype file of Hinxton3 available at Genetic Genealogy Tools. For more information and some speculation about these genomes see my earlier blog post here.

Despite the exaggerated North Sea score in the Eurogenes K15, Hinxton3 could easily pass for a present-day Briton from the eastern coast of England or Scotland, albeit with a stronger than usual pull towards Scandinavia. Indeed, the f3-statistics show that it shares most genetic drift with the British and Icelanders from Eurogenes and Human Origins, respectively.

Hinxton2, or ERS389796, is one of five ancient English genomes stored at the Sequence Read Archive under accession number ERP003900. However, this analysis is based on the genotype file of Hinxton2 available at Genetic Genealogy Tools. For more information and some speculation about these genomes see my earlier blog post here.

Interestingly, f3-statistics in the form f3(Mbuti;Hinxton2,Test) show that Hinxton2 shares most genetic drift with present-day Danes and Norwegians. Please refer to the relevant spreadsheets below.

Sunday, October 12, 2014

Several ancient genomes have been posted online as text files and uploaded to GEDmatch over the last couple of weeks, and many more are likely to follow in the future. A lot of people have already taken this opportunity to analyze these files with various online ancestry tools, usually DIY calculators.

That's actually not a bad way of doing things, as long as everyone's aware that almost all of these calculators produce biased results. They produce biased results because they violate a very basic rule of science, which is this:

Do not test more than one variable at a time.

Obviously, the variable we want to test with these calculators is ancestry. However, when the reference samples are tested in a different way to the test samples, which is what usually happens, then this adds another variable to the proceedings. As a result, we simply can't compare the results of the reference samples to those of the test samples.

I know that a lot of people find this difficult to grasp, and many just seem hell bent on not grasping it. However, anyone who isn't completely insane, and takes five minutes out of their day to try and understand the concepts involved, has to agree that this is a real problem. It can be proven empirically, like I did over two years ago (see here).

I suspect that a lot of confusion has been caused by the fact that the people who were used as reference samples in the making of the various DIY calculators saw highly accurate results when running them, and so assumed everything was fine. The accuracy of the DIY calculators for such people is indeed impressive, and I show that at the link above, but unfortunately the story is very different for everyone else.

Here's the good news: the Eurogenes calculators don't suffer from the calculator effect. That's because the reference samples are treated in the same way as the test samples, so there's only one variable: ancestry. What this means is that when you run a modern or ancient genome with a Eurogenes calculator you can confidently compare the result to those of the reference samples (provided enough SNPs are used), and then be able to make sensible inferences about its genetic origins.

Wednesday, October 8, 2014

I've just added an ancient sample from Hinxton, England, to my burgeoning ancient genomes collection. It's a pre-publication release freely available here as ERS389795. Thanks to Felix C. for breaking the news. We've both called this sample Hinxton1.

Unfortunately, its archeological context is a mystery to me, but it's possibly one of the ancient genomes mentioned in the recent Schiffels et al. ASHG abstract (see here).

In terms of genome-wide genetic structure, Hinxton1 is most similar to present-day Orcadians, Irish, western Scots, Icelanders and western Norwegians, more or less in that order. However, it's fairly distinct from the modern inhabitants of England, or at least those in my datasets, who mostly come from Kent and Cornwall.

Please note, this analysis features two different datasets: Eurogenes and Human Origins. Eurogenes, which is my own dataset, includes more populations than Human Origins, and is based on SNPs used in commercial ancestry and medical work. On the other hand, Human Origins shows a more varied sampling strategy, and is based on SNPs specifically chosen for population genetics.

Friday, October 3, 2014

I've just spotted a few interesting extras in the final draft of Lazaridis et al. that appeared in Nature last month, including this quote from page 126 of the freely available supp info:

The finding of high ANE ancestry in the North Caucasus might suggest that the Caucasus is a potential source of this type of ancestry in Europe. However, when we try to fit present-day Europeans as a 3-way mixture of a North Caucasian population+EEF+WHG in the structure of Fig. S14.20 this model is successful for only 5 populations (Bergamo, Bulgarian, Italian_South, Spanish_North, Tuscan using Lezgins as a sister group to the admixing population). Admixture from the Caucasus would need to be substantial to account for observed ANE levels in Europe (e.g., for a European population with ~15% ANE ancestry, almost half of its ancestry must come from a Lezgin-like population with ~29% ANE ancestry; this would account for the ANE ancestry but would greatly dilute its WHG-related ancestry, and yet present-day Europeans have increased affinity to WHG in Extended Data Fig. 4 relative to Stuttgart).

This was rather obvious anyway, but I know that there are a lot of people online who cherish the notion that Europe was invaded in a big way by groups from the Caucasus and/or Anatolia during the Bronze Age, and I'm guessing this paragraph was a response to the comments that the authors received from these people during the public review process.

Indeed, the updated supp info also has a couple of new Principal Component Analyses (PCA) of West Eurasian populations, with which Lazaridis et al. underline the point that most Europeans and Near Easterners form "two discontinuous clines" in such analyses (pages 76-80). I could be wrong, but the impression I get is that they're again communicating how very improbable it is for most Europeans to harbor any Near Eastern and Caucasian admixture that post dates the Neolithic transition.

This of course leaves pre-Turkic far Eastern Europe, Western Siberia and/or Central Asia as the source(s) of the ANE-rich population movements that apparently had such a profound impact on most of the European gene pool after the final Neolithic.